Differential modulation of polyunsaturated fatty acids in patients with myocardial infarction treated with ticagrelor or clopidogrel.

Abstract

Untargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P2Y12 inhibitors. We identified a signature that discriminates patients, which involves polyunsaturated fatty acids (PUFAs) and particularly the omega-3 fatty acids docosahexaenoate and eicosapentaenoate. The known cardiovascular benefits of PUFAs could contribute to the efficacy of ticagrelor. Our work, beyond pointing out the high relevance of untargeted metabolomics in evaluating response to treatment, establishes PUFA metabolism as a pathway of clinical interest in the recovery path from MI.

• Authors: Karla N Samman, Pamela Mehanna, Emad Takla, Jean-Christophe Grenier, Mark Y Chan, Renato D Lopes, Megan Lee Neely, Tracy Y Wang, L Kristin Newby, Richard C Becker, Marie Lordkipanidzé, Matthieu Ruiz, Julie G Hussin, E Marc Jolicœur
• Journal: Cell reports. Medicine (Cell Rep Med) Vol. 2 Issue 6 Pg. 100299 (06 15 2021) ISSN: 2666-3791 [Electronic] United States
• PMID: 34195679 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors.

Chemical References

• Fatty Acids, Unsaturated
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Clopidogrel
• Ticagrelor

Topics

• Acute Coronary Syndrome (drug therapy, metabolism, pathology)
• Aged
• Blood Platelets (drug effects, metabolism)
• Clopidogrel (therapeutic use)
• Fatty Acids, Unsaturated (agonists, metabolism)
• Female
• Humans
• Lipid Metabolism (drug effects)
• Male
• Metabolomics (methods)
• Middle Aged
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Platelet Aggregation Inhibitors (therapeutic use)
• Purinergic P2Y Receptor Antagonists (therapeutic use)
• Ticagrelor (therapeutic use)
• Treatment Outcome